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Chronic Low-Dose Cadmium Exposure Impairs Cutaneous Wound Healing With Defective Early Inflammatory Responses After Skin Injury.
- Source :
- Toxicological Sciences; Oct2017, Vol. 159 Issue 2, p327-338, 12p, 1 Chart, 6 Graphs
- Publication Year :
- 2017
-
Abstract
- Impairment of the immune system is a developing concern in evaluating the toxicity of cadmium(Cd). In the present study, we investigated if Cd could impair cutaneous wound healing through interfering with inflammation after injury.We found that exposure ofmice to CdCl<subscript>2</subscript> through drinking water at doses of 10, 30, and 50mg/l for 8weeks significantly impaired cutaneous wound healing. Chronic 30mg/l CdCl<subscript>2</subscript> treatment elevatedmurine blood Cd level comparable to that of low dose Cd-exposed humans, had no effect on blood total and differential leukocyte counts, but reduced neutrophil infiltration, chemokines (CXCL1 and CXCl<subscript>2</subscript>), and proinflammatory cytokines (TNFa, IL-1b, and IL-6) expression in wounded tissue at early stage after injury.Wounded tissue homogenates from CdCl<subscript>2</subscript>-treatedmice had lower chemotactic activity for neutrophils than those fromuntreatedmice.Mechanistic studies showed that chronic Cd treatment suppressed ERK1/2 and NF-jB p65 phosphorylation in wounded tissue at early stage after injury. Compared with neutrophils isolated fromuntreatedmice, neutrophils from CdCl<subscript>2</subscript> treatedmice and normal neutrophils treated with CdCl<subscript>2</subscript> in vitro both had lower chemotactic response, calciummobilization and ERK1/2 phosphorylation upon chemoattractant stimulation. Collectively, our study indicate that chronic low-dose Cd exposure impaired cutaneous wound healing by reducing neutrophil infiltration through inhibiting chemokine expression and neutrophil chemotactic response, and suppressing proinflammatory cytokine expression. Cdmay suppress chemokine and proinflammatory expression through inactivating ERK1/2 and NF-jB, and inhibit neutrophil chemotaxis by attenuating calciummobilization and ERK1/2 phosphorylation in response to chemoattractants. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10966080
- Volume :
- 159
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Toxicological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 125456472
- Full Text :
- https://doi.org/10.1093/toxsci/kfx137